Furthermore, this “two-signal” requirement for stable IDO induction, with an immunogenic trigger such as TLR ligands or IFN constituting “signal one” and an immunosuppressive trigger such as IL-10, TGFβ or kynurenine as “signal two”, may potentially provide an explanation for the long-term enigmatic paradox concerning the detrimental versus protective role of IFNγ in MS and EAE, as IFNγ may possibly have differential effects on different cell types (such as autoreactive T cells versus DCs) and/or in different disease stages39,40. Here, TGFB1 is linked to myeloid sarcoma.